Our overall goal is to develop, optimize, and validate innovative and improved MRI techniques for the diagnosis, early detection, treatment monitoring, and investigation of neurodegenerative diseases (ND), which will be made available to the scientific community. These techniques will provide increased signal and contrast to noise and resolution per unit scan time, reduced susceptibility and motion artifacts, in order to improve disease detection. The techniques include improved MRI/MRS acquisition, image reconstruction methods, and processing/analysis methods for high magnetic field MRI/MRS. The results will be distributed to the scientific community. This proposal represents a continuation of collaborative work between MRI physicists, computer scientists and clinical investigators aimed at a single theme: neurodegenerative diseases. The specific aims of this Biotechnology Research Resource are to develop, optimize and validate: 1) MR acquisition methods for structural, perfusion, and diffusion spectrum MRI, and spectroscopic imaging. The focus of the work will be on developing new sequences to capture alterations of brain structure, physiology (blood flow), and metabolism with improved sensitivity and resolution and increased reliability and precision. 2) Image reconstruction methods for increasing speed, efficiency, and quantitative accuracy of MRI. The focus of the work will be on exploiting the properties of Bayesian prior information for either deterministic or statistical image modeling to improve image quality, signal-to-noise and resolution. 3) MR image processing techniques for extraction of accurate and reproducible anatomical information. The focus of the work will be on developing novel tissue segmentation techniques and new spatial normalization strategies. 4) We will utilize these improvements in collaborative/service projects concerning NDs 5) We will provide training for investigators and staff within and outside the Research Resource. 6) We will disseminate the knowledge, tools, and data generated by this resource The significance of this project is several fold: First, the prevalence of NDs is rapidly growing due to aging of the population and methods for early detection are urgently needed. Second, due to advances in basic knowledge, treatments for NDs are under development and sensitive methods to determine treatment response are required. This Research Resource will develop improved techniques for clinical diagnosis, early detection, and monitoring of progression and treatment effects of common NDs, and these technical advances will also be applicable to many other clinical problems.